Fri Nov 04 2022

87 articles - From Friday Oct 28 2022 to Friday Nov 04 2022

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Guidelines

Guidelines, position statements, white papers, technical reviews, consensus statements, etc…

Am J Hematol

International Consensus Classification for Myeloid Neoplasms At-A-Glance.

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Ann Oncol

Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

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Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO Clinical Practice Guideline.

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Blood Adv

Chronic GvHD NIH Consensus Project Biology Task Force: Evolving path to personalized treatment of chronic GvHD.

Capitalizing on progress made to date, the field is now focused on establishing personalized treatment approaches. The manuscript's intent is to concisely review recent knowledge gained and formulate a path towards patient-specific cGvHD therapy.

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CA Cancer J Clin

Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer.

Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

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Meta-analysis

meta-analyses and systematic reviews


Original articles

RCT, clinical trials, retrospective studies, etc…

Am J Hematol

A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes.

Median OS was 12.6 months. Venetoclax + azacitidine shows activity in patients with R/R MDS following prior HMA therapy failure and provides clinically meaningful benefits, including HI and TI, and encouraging OS.

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Closing Remarks.

The notion of complement inhibition is awesome, but some of the results achieved in therapy of serious diseases have been spectacular. Currently several pharmacological options are already available, and more are in the offing: it will be ever more important that they are optimally used in terms of safety and of therapeutic efficacy.

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Proposed risk-scoring model for estimating the prognostic impact of 1q gain in patients with newly diagnosed multiple myeloma.

Hence, patients with +1q are a heterogeneous group of high-risk patients, therefore underlining the necessity for their re-stratification. The proposed simple risk-scoring model can estimate the outcomes of patients with +1q, which may help guide risk-adapted treatment for such patients.

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Blood

A RUNX1-FPDMM rhesus macaque model reproduces the human phenotype and predicts challenges to curative gene therapies.

Bone marrows developed megakaryocytic dysplasia similar to human FPDMM, and CD34+ HSPCs showed impaired in vitro megakaryocytic differentiation, with a striking defect in polyploidization. In conclusion, the lack of a competitive advantage for wildtype or control-edited HSPCs over RUNX1 heterozygous-mutated HSPCs long-term in our preclinical model suggests that gene correction approaches for FPDMM will be challenging, particularly to reverse MDS/AML predisposition and thrombopoietic defects.

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Bispecific antibodies for the treatment of B-cell lymphoma: Promises, unknowns and opportunities.

Much work remains to be done to define the optimal setting in which to deploy these drugs for B-NHL treatment, their ideal combination partners, strategies to minimize toxicity and, perhaps most importantly, pharmacodynamic biomarkers of response and resistance. In this review, we provide an update on BsAb development in B-NHL, from discovery to clinical applications, highlighting the achievements, limitations and future directions of the field.

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C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse.

This cell-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as an adverse prognostic marker of AML which orchestrates cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

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Dietary iron restriction protects against vaso-occlusion and organ damage in sickle cell disease.

These findings provide strong evidence for the therapeutic potential of manipulating iron homeostasis and the gut microbiome to ameliorate SCD pathophysiology. Many treatments under development focus on lowering the systemic iron concentration to relieve disease complications, and our data suggest that iron-induced changes in microbiota load and gut integrity are related and novel therapeutic targets.

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Engineered and Banked iPSCs for advanced NK and T cell immunotherapies.

In this review, we will highlight recent progress in iPSC editing and guided differentiation to develop NK and T cell products for immunotherapy. We will also discuss some of the potential barriers that remain in unleashing the full potential of iPSC-derived cytotoxic effector cells in the adoptive transfer setting and how some of these limitations may be overcome through gene editing.

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Germline DDX41 mutations define a unique subtype of myeloid neoplasms.

Finally, outcomes were not affected by the conventional risk stratifications including the revised/molecular International Prognostic Scoring System (IPSS-R/M). Our findings establish that DDX41-mutated MDS defines a unique subtype of MNs that is distinct from other MNs.

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How I diagnose and treat atypical hemolytic uremic syndrome.

Nevertheless, long-term management of atypical HUS is increasingly individualized and life-long C5 blockade is no more a paradigm that applies to al patients with this disease. The potential benefit of complement blockade in other forms of HUS, notably secondary HUS, remains uncertain.

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How I Treat Anemia with Red Blood Cell Transfusion and Iron.

Iron-restricted erythropoiesis is a common cause of anemia severe enough to be considered for red blood cell transfusion but diagnosis and management of absolute iron deficiency anemia, the anemia of inflammation with functional iron deficiency, or their combination may be problematic. Intravenous iron therapy is generally the treatment of choice for absolute iron deficiency in patients with complex medical disorders, with or without coexisting functional iron deficiency.

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Hydroxyurea for Secondary Stroke Prevention in Children with Sickle Cell Anemia in Nigeria:a Randomized Controlled Trial.

For children with SCA in low-income settings, without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention. The ID number assigned to the study is NCT02675790.

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Interventions and outcomes of multiple myeloma patients receiving salvage treatment after BCMA-directed CAR T therapy.

Patients with multiple myeloma who relapse after BCMA-directed CAR T have a limited prognosis but can be potentially treated with multiple lines of salvage therapy. T cell-engaging therapies appear to maintain pronounced clinical activity in this setting.

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Long-term risk of relapse in immune-mediated Thrombotic Thrombocytopenic Purpura and the role of anti-CD20 therapy.

We reviewed patients with iTTP having >3 years follow-up over 10-years in the United Kingdom to identify patient characteristics for relapse, assess relapse rates and patterns, and response to anti-CD20 therapy in those with ADAMTS13 relapses (ADAMTS13 activity 20%. Anti-CD20 therapy was demonstrated to be an effective long-term treatment regardless of relapse pattern and there was no loss of this treatment response following subsequent treatment episodes.

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Molecular Determinants of Clinical Outcomes In a Real-World Diffuse Large B-cell Lymphoma Population.

DZsigpos and ABC-DLBCL had shorter diagnosis-to-treatment interval (DTI) than GCB-DLBCL, with this metric being associated with outcome. In conclusion, DZsig expression extends beyond HGBCL-DH-BCL2 and captures a poor-prognosis DLBCL subgroup with short DTI, including patients unidentifiable by routine FISH testing, that should be considered for treatment intensification or novel therapies in prospective trials.

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Noncanonical ß-catenin interactions promote leukemia-initiating activity in early T-cell acute lymphoblastic leukemia.

Additionally, gene expression data at the single-cell level of leukemic cells of primary patients at the diagnosis and minimal residual disease (MRD) up to 30 days from the standard treatments reveal that the expression of ß-Catenin and FOXO3 dependent genes is present in the CD82+CD117+ cell fraction, which is substantially enriched with LICs in MRD as well as in early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). These findings highlight key functional roles for ß-Catenin and FOXO3 and suggest novel therapeutic strategies to eradicate aggressive cell subsets in T-ALL.

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Regulation of iron homeostasis by hepatocyte TFR1 requires HFE and contributes to hepcidin suppression in ß-thalassemia.

Together, our data suggest that the major nonredundant function of hepatocyte TFR1 in iron homeostasis is to interact with HFE to regulate hepcidin. This regulatory pathway is modulated by serum iron and contributes to hepcidin suppression and iron overload in murine ß-thalassemia.

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Single-cell methods in myeloproliferative neoplasms - old questions, new technologies.

Therefore, it is not surprising that many of the groundbreaking technological advances in single-cell omics have been pioneered by their application in MPNs. In this review article, we explore how single-cell approaches have provided transformative insights into MPN disease biology, that are broadly applicable across human cancers, and discuss how these studies might be swiftly translated into clinical pathways and may eventually underpin precision medicine.

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Therapeutic activity of GARP:TGF-ß1 blockade in murine primary myelofibrosis.

These therapeutic effects, accompanied by increased IFN-g signals in the spleen, were lost upon CD8 T cell depletion. Our results suggest that selective blockade of TGF-b1 activation by GARP-expressing Tregs increase a CD8 T cell-mediated immune reaction that limits transformed cell expansion, providing a novel approach that could be tested to treat patients with myeloproliferative neoplasms.

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Blood Adv

ADAMTS13 conformation and immunoprofiles in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura.

While this profile did not impact the one-year TTP-related mortality rate, patients with autoantibodies against al 6 ADAMTS13 fragments had a higher risk for TTP-related death than other patients (p=0.02). We here validated open ADAMTS13 as a novel biomarker for acute iTTP and determined the dominant immunoprofiling in the Japanese cohort, contributing to setting up the diagnosis and managing guidelines across different ethnic cohorts and to developing ADAMTS13 variants that do not bind to the anti-CS autoantibodies.

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AKT supports the metabolic fitness of multiple myeloma cells by restricting FOXO activity.

Moreover, the FOXO-dependent repression of glycolysis- and TCA-associated genes correlates with a favorable prognosis in a large MM patient cohort. Our data suggest that repression of FOXO by AKT is essential to sustain glycolysis and the TCA cycle activity in MM cells, and as such predicts patient survival.

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Baseline radiomics features and MYC rearrangement status predict progression in aggressive B-cell lymphoma.

PPV was highest for the MYC+radiomics model (50.0%) and increased with 20% compared to the IPI (29.6%). Adding radiomics features improved model performance and PPV and can therefore aid in identifying poor prognosis patients.

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CD11c regulates neutrophil maturation.

Deficiency of IQGAP1 largely impaired their maturation and effector functions associated with higher apoptosis under neutrophil differentiation stimulants. Taken together, we discovered that CD11c was critical for the regulation of neutrophil maturation via interacting with IQGAP1 and considered a potential target for sepsis treatment.

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Clinical outcomes associated with NPM1 mutations in patients with relapsed or refractory AML.

Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS: 15.8 vs 4.6 months, P=0.05; median OS: 14.7 vs 5.9 months, P=0.02). In conclusion, NPM1 mutational status has minimal impact on prognosis in relapsed or refractory AML, therefore equally requiring novel treatment strategies to improve outcomes in this entity.

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Dasatinib/Prednisone Induction Followed by Blinatumomab/Dasatinib in Ph+ Acute Lymphoblastic Leukemia.

Although longer follow up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial is registered at as NCT02143414.

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Factor VIII mutated with Lys1813Ala within the factor IXa-binding region enhances intrinsic coagulation potential.

In the tail-clip assay of HA-mice, FVIII-K1813A showed a 2-4-fold higher hemostatic potential than WT. FVIII-K1813A, with higher FIXa binding affinity, enhances the global coagulation potential due to the stability of FVIII/FVIIIa molecules.

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FBXW7ß isoform drives transcriptional activation of the proinflammatory TNF cluster in human pro-B cells.

This signature contained several members of the TNF superfamily, including those comprising the HLA Class III cluster (LTB, LST1, NCR3, LTA, and NFKBIL1). Our findings suggest that FBXW7ß expression drives proinflammatory responses, which could contribute to normal B-cell development, leukemogenesis and responses to anti-cancer therapies.

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miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells.

Overall, our study identified DDX6 as a post-transcriptional regulator that is required for AML survival. We proposed the regulatory link between miR-148a-3p and DDX6 as a potential therapeutic target in leukemia.

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The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Thus, fetal transfusions enable survival of patients with ATM with normal neurodevelopment even in patients presenting with hydrops. Non-directive prenatal counseling of expectant parents should include the option of IUTs.

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Blood Cancer J

Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma.

In multiple myeloma, prophylactic G-CSF was not used; patients were stratified by early G-CSF exposure (=2 days vs =3 days after CAR T or no exposure), with no significant difference in toxicities. Future trials should clarify the optimal G-CSF strategy to improve outcomes after CAR T.

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Prognostic impact of ASXL1 mutations in chronic phase chronic myeloid leukemia.

In a multivariate analysis, ASXL1 mutation was the only independent risk factor associated with worse EFS in chronic phase CML with a hazard ratio of 4.25 (95% CI 1.59-11.35, P=0.004). In conclusion, mutations in ASXL1 are associated with worse outcomes when detected in chronic phase CML.

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Pure (acute) erythroid leukemia: morphology, immunophenotype, cytogenetics, mutations, treatment details, and survival data among 41 Mayo Clinic cases.

Treatment details were available in 29 patients: hypomethylating agent (HMA) alone (n=5), HMA+venetoclax (n=12), intensive chemotherapy (n=4), supportive care/other (n=8); no responses or allogeneic stem cell transplants were documented, and al patients died at a median 1.8 months (range 0.2-9.3). The current study highlights a consistent and reproducible set of morphologic and genetic characteristics that identify PEL as a distinct AML variant whose dismal prognosis requires urgent attention.

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Haematologica

A novel SART3::RARG fusion gene in acute myeloid leukemia with acute promyelocytic leukemia phenotype and differentiation escape to retinoic acid.

Not available.

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An objective assessment in newly diagnosed multiple myeloma to avoid treatment complications and strengthen therapy adherence.

We performed this study in 250 consecutive MM patients who underwent a prospective fitness assessment at our center, yet received induction protocols based on physicians' judgement. DR, serious adverse events (SAEs), response, progression free- (PFS) and overall survival (OS) were compared in fitness (fit, intermediate-fit, frail), age (.

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B and T cell acute lymphoblastic leukemia evade chemotherapy at distinct sites in the bone marrow.

A subset of slowly dividing ALL cells was transiently detected upon short-term chemotherapy, but not at residual disease after chemotherapy, challenging the notion that ALL cells escape treatment by direct induction of a dormant state in the niche. These lineage-dependent differences point to niche interactions that may be more specifically exploitable to improve treatment.

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Delayed hemolytic transfusion reaction in children with sickle cell disease: first five-year retrospective study in mainland France.

Not available.

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Do older patients truly benefit from advances in myeloma care?

Not available.

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Genomics improves risk stratification of adults with T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials.

The combined WOG signature and MRD on day +35 allowed risk-stratification of T-ALL into standard or high-risk groups with significantly different 5-year overall survival (OS) (95% confidence interval [CI]) of 52% (37-67 %) and 17% (1-33%), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.

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Improved survival in myeloma patients- a nationwide registry study of 4647 patients =75 years treated in Denmark and Sweden.

Compared to the randomized controlled trials that guide the treatment of non-transplant eligible patients, we find a higher proportion of patients =75 years and presenting with ISS III in real world data. Nevertheless, response rates and survival are increasing, reflecting that modern treatment regimens are effective and well tolerated, also in elderly MM patients in real-world populations.

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International multicentre retrospective analysis of thiotepa-based autologous stem cell transplantation for secondary central nervous system lymphoma.

Not available.

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Prognostic impact of pre-treatment immunoglobulin clonal composition in pediatric Blymphoblastic leukemia.

Not available.

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Therapeutic potential of ß-lactam ceftriaxone for chronic pain in sickle cell disease.

Not available.

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Unique pathologic features and gene expression signatures distinguish blastoid high-grade B-cell lymphoma from B acute lymphoblastic leukemia/lymphoma.

Not available.

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Lancet Haematol

Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial.

Interpretation Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone for induction therapy improved rates of MRD negativity with no new safety signals in patients with newly diagnosed transplantation-eligible multiple myeloma. Funding Sanofi and Bristol Myers Squibb (Celgene).

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Leukemia

An MDM2 degrader for treatment of acute leukemias.

In particular, MS3227 treatment was shown to downregulate MCL-1, a known mediator of resistance to venetoclax. A PROTAC-based approach may provide a means of improving MDM2 inhibition to gain greater therapeutic potential in AML.

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Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients.

Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1-3 cycles.

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Outcome of chimeric antigen receptor T-cell therapy following treatment with inotuzumab ozogamicin in children with relapsed or refractory acute lymphoblastic leukemia.

No difference in day 28 minimal residual disease negative complete response rate, 12-month OS/EFS, or incidence of CD19-positive or -negative relapses was observed among patients receiving InO before or after apheresis. Compared to published data for patients treated with CART-19 therapy without prior InO exposure, response and OS/EFS for patients treated with InO prior to CART-19 are similar.

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Thromb Haemost

Visualization of Domain- and Concentration-Dependent Impact of Thrombomodulin on Differential Regulation of Coagulation and Fibrinolysis.

TAFI activation might be affected by attenuation in thrombin activity after the clot formation phase. These findings suggest that the spatiotemporal balance between the anticoagulant and antifibrinolytic potential of TM is controlled in domain- and concentration-dependent manners.

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Reviews&Editorials

Plenty of the editorials are available as full text through the publisher website using the provided link

Blood

A Tet-a-Tet in T follicular helper cell lymphoma.

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Claiming the mantle of the brain.

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KMT2A-rearranged leukemia: the shapeshifter.

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Safer steps on a narrow path.

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Sickle cell inflammation: is HbS the answer?

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J Hematol Oncol

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications.

Targeting Warburg metabolism would be a promising method for the treatment of CRC. In this review, we summarize information about the roles of Warburg effect in tumor microenvironment to elucidate the mechanisms governing Warburg effect in CRC and to identify novel targets for therapy.

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Lancet Haematol

Iron deficiency anaemia-an ongoing challenge.

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Leukemia

Pathogenesis and management of accelerated and blast phases of chronic myeloid leukemia.

Regimens including venetoclax in myeloid BP or inotuzumab ozogamicin or blinatumomab in lymphoid BP might lead to deeper and longer responses, facilitating potentially curative allo-SCT for patients with CML-BP once CP is achieved. Newer agents and novel combination therapies are further expanding the therapeutic arsenal in advanced phase CML.

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The universal stem cell.

Thus, there is a universal stem cell in the marrow which alters its differentiation potential as it progresses through cell cycle. This potential is expressed when it resides in tissues compatible with its differentiation potential, at a particular point in cell cycle transit, or when it interacts with vesicles from that tissue.

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Miscellaneous

misc publications eg case reports, tools of the trade, images of the month, etc…

Blood

light chain-expressing hematogones in a patient with -restricted CLL and multiple myeloma on daratumumab therapy.

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Burkitt lymphoma genomic discovery studies, drivers and validation.

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Concerning data inconsistencies in Burkitt lymphoma genome study.

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Metastatic angiosarcoma in a bone marrow biopsy.

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Revisiting Co-existing Chromosomal Abnormalities in NPM1-mutated AML in Light of the Revised ELN 2022 classification.

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Blood Adv

Patient reported outcomes in children with sickle cell disease at presentation for an acute pain episode.

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Pevonedistat with azacitidine in older patients with TP53-mutated AML: a phase 2 study with laboratory correlates.

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Reduced FVIII recovery associated with anti-FVIII PEG antibodies after BNT162b2 SARS-CoV-2 vaccination.

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Sustained hematologic remission after discontinuation of sutimlimab treatment in patients with cold agglutinin disease.

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Haematologica

Images from the Haematologica Atlas of Hematologic Cytology: Gaucher disease.

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What doesn't kill you makes you stronger - bcl-2 promotes survival independent of proliferation.

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J Hematol Oncol

Retraction Note: Genomic amplification and high expression of EGFR are key targetable oncogenic events in malignant peripheral nerve sheath tumor.

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Lancet Haematol

Burning out-whose responsibility is it?

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Isolated IgG4-related disease of the left maxillary antrum.

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Maximising response depth is important in multiple myeloma.

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Place-of-care manufacturing of gene therapies.

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Rahul Bhargava: making bone marrow transplantation accessible in India.

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Leukemia

Clinical characteristics and outcomes of B-cell precursor ALL with MEF2D rearrangements: a retrospective study by the Ponte di Legno Childhood ALL Working Group.

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UTX loss alters therapeutic responses in KMT2A-rearranged acute myeloid leukemia.

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Thromb Haemost

Current Concepts: Comprehensive "Cardiovascular Health" Rehabilitation-An Integrated Approach to Improve Secondary Prevention and Rehabilitation of Cardiovascular Diseases.

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Does Fibrinolytic Strategy of Pulmonary Embolism International ThrOmbolysis (PEITHO)-3 Trial Need More Strong Evidence?

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Letters&Replies

Letters to the editors and authors’ replies

Am J Hematol

COVID-19 mRNA Vaccine associated Cerebral Venous Thrombosis: Rare Adverse Event or Coincidence?

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Pagophagia and Restless Legs Syndrome are Highly Associated with Iron Deficiency and Should Be Included in Histories Evaluating Anemia.

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Blood Cancer J

High efficacy of Azacitidine plus HAG in acute myeloid leukemia: an open-label, single-arm, multi-center, phase 2 study.

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J Hematol Oncol

Pembrolizumab combined with low-dose cyclophosphamide and intra-tumoral injection of the toll-like receptor 4 agonist G100 in patients with advanced pretreated soft tissue sarcoma: results from the PEMBROSARC basket study.

TLR4 stimulation might have both antitumor and pro-tumor consequences.: This study was registered with ClinicalTrial. gov, number NCT02406781.

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